A second species-specific element in addition to the human interferon gamma receptor is necessary for biological responsiveness to human interferon gamma. The gene for this element maps to the distal region of 21q22.1 in the same area as the gene for the human interferon alpha/beta receptor. The primary goal of this proposal is the isolation and characterization of the interferon gamma response gene and gene product which should provide insights into the action of interferons and may increase our understanding of the immunological deficiencies associated with Down syndrome.